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Physiology - NEETMDS- courses
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Physiology

The hepatic portal system

The capillary beds of most tissues drain into veins that lead directly back to the heart. But blood draining the intestines is an exception. The veins draining the intestine lead to a second set of capillary beds in the liver. Here the liver removes many of the materials that were absorbed by the intestine:

  • Glucose is removed and converted into glycogen.
  • Other monosaccharides are removed and converted into glucose.
  • Excess amino acids are removed and deaminated.
    • The amino group is converted into urea.
    • The residue can then enter the pathways of cellular respiration and be oxidized for energy.
  • Many nonnutritive molecules, such as ingested drugs, are removed by the liver and, often, detoxified.

The liver serves as a gatekeeper between the intestines and the general circulation. It screens blood reaching it in the hepatic portal system so that its composition when it leaves will be close to normal for the body.

Furthermore, this homeostatic mechanism works both ways. When, for example, the concentration of glucose in the blood drops between meals, the liver releases more to the blood by

  • converting its glycogen stores to glucose (glycogenolysis)
  • converting certain amino acids into glucose (gluconeogenesis).

Lipids:

  • about 40% of the dry mass of a typical cell
  • composed largely of carbon & hydrogen
  • generally insoluble in water
  • involved mainly with long-term energy storage; other functions are as structural components (as in the case of phospholipids that are the major building block in cell membranes) and as "messengers" (hormones) that play roles in communications within and between cells
  • Subclasses include:
    • Triglycerides - consist of one glycerol molecule + 3 fatty acids (e.g., stearic acid in the diagram below). Fatty acids typically consist of chains of 16 or 18 carbons (plus lots of hydrogens).
    • phospholipids - Composed of 2 fatty acids, glycerol, phosphate and polar groups , phosphate group (-PO4) substitutes for one fatty acid & these lipids are an important component of cell membranes

steroids - have 4 rings- cholesterol, some hormones, found in membranes include testosterone, estrogen, & cholesterol

 Pain, Temperature, and Crude Touch and Pressure

General somatic nociceptors, thermoreceptors, and mechanoreceptors sensitive to crude touch and pressure from the face conduct signals to the brainstem over GSA fibers of cranial nerves V, VII, IX, and X.

The afferent fibers involved are processes of monopolar neurons with cell bodies in the semilunar, geniculate, petrosal, and nodose ganglia, respectively.

The central processes of these neurons enter the spinal tract of V, where they descend through the brainstem for a short distance before terminating in the spinal nucleus of V.

Second-order neurons then cross over the opposite side of the brainstem at various levels to enter the ventral trigeminothalamic tract, where they ascend to the VPM of the thalamus.

Finally, third-order neurons project to the "face" area of the cerebral cortex in areas 3, 1, and 2 .

Discriminating Touch and Pressure

Signals are conducted from general somatic mechanoreceptors over GSA fibers of the trigeminal nerve into the principal sensory nucleus of V, located in the middle pons.

Second-order neurons then conduct the signals to the opposite side of the brainstem, where they ascend in the medial lemniscus to the VPM of the thalamus.

 Thalamic neurons then project to the "face" region of areas 3, I, and 2 of the cerebral cortex.

 Kinesthesia and Subconscious Proprioception

Proprioceptive input from the face is primarily conducted over GSA fibers of the trigeminal nerve.

The peripheral endings of these neurons are the general somatic mechanoreceptors sensitive to both conscious (kinesthetic) and subconscious proprioceptive input.

Their central processes extend from the mesencephalic nucleus to the principal sensory nucleus of V in the pons

The subconscious component is conducted to the cerebellum, while the conscious component travels to the cerebral cortex.

Certain second-order neurons from the principal sensory nucleus relay proprioceptive information concerning subconscious evaluation and integration into the ipsilateral cerebellum.

Other second-order neurons project to the opposite side of the pons and ascend to the VPM of the thalamus as the dorsal trigeminothalamic tract.

Thalamic projections terminate in the face area of the cerebral cortex.

Levels of Organization:

CHEMICAL LEVEL - includes all chemical substances necessary for life (see, for example, a small portion - a heme group - of a hemoglobin molecule); together form the next higher level

CELLULAR LEVEL - cells are the basic structural and functional units of the human body & there are many different types of cells (e.g., muscle, nerve, blood)

TISSUE LEVEL - a tissue is a group of cells that perform a specific function and the basic types of tissues in the human body include epithelial, muscle, nervous, and connective tissues

ORGAN LEVEL - an organ consists of 2 or more tissues that perform a particular function (e.g., heart, liver, stomach)

SYSTEM LEVEL - an association of organs that have a common function; the major systems in the human body include digestive, nervous, endocrine, circulatory, respiratory, urinary, and reproductive.

There are two types of cells that make up all living things on earth: prokaryotic and eukaryotic. Prokaryotic cells, like bacteria, have no 'nucleus', while eukaryotic cells, like those of the human body, do.

1.Rhythmicity ( Chronotropism ) :  means the ability of heart to beat regularly ( due to repetitive and stable depolarization and repolarization )  . Rhythmicity of heart is a myogenic in origin , because cardiac muscles are automatically excited muscles and does not depend on the nervous stimulus to initiate excitation and then contraction . The role of nerves is limited to the regulation of the heart rate and not to initiate the beat.

There are many evidences that approve the myogenic and not neurogenic origin of the rhythmicity of cardiac muscle . For example :
-  transplanted heart continues to beat regularly without any nerve supply.
-  Embryologically the heart starts to beat before reaching any nerves to them.
-  Some drugs that paralyze the nerves ( such as cocaine ) do not stop the heart in given doses.

Spontaneous rhythmicity of the cardiac muscle due to the existence of excitatory - conductive system , which is composed of self- exciting non-contractile cardiac muscle cells . The SA node of the mentioned system excites in a rate , that is the most rapid among the other components of the system ( 110 beats /minute ) , which makes it the controller or ( the pacemaker ) of the cardiac rhythm of the entire heart.

Mechanism , responsible for self- excitation in the SA node and the excitatory conductive system  is due to the following properties of the cell membrane of theses cells :
1- Non-gated sodium channels
2- Decreased permeability to potassium
3- existence of slow and fast calcium channels.

These properties enable the cations ( sodium through the none-gated sodium voltage channels , calcium through calcium slow channels) to enter the cell and depolarize the cell membrane without need for external stimulus.

The resting membrane potential of non-contractile cardiac cell is -55 - -60 millivolts ( less than that of excitable nerve cells (-70) ) . 

The threshold is also less negative than that of nerve cells ( -40 millivolts ).

The decreased permeability to potassium from its side decrease the eflux  of potassium during the repolarization phase of the pacemaker potential . All of these factors give the pacemaker potential its characteristic shape

Repeating of the pacemaker potential between the action potentials of contractile muscle cells is the cause of spontaneous rhythmicity of cardiac muscle cells.

Factors , affecting the rhythmicity of the cardiac muscle :


I. Factors that increase the rate ( positive chronotropic factors) :
1. sympathetic stimulation : as its neurotransmitter norepinephrine increases the membrane permeability to sodium and calcium.
2. moderate warming : moderate warming increases temperature by 10 beats for each 1 Fahrenheit degree increase in body temperature, this due to decrease in permeability to potassium ions in pacemaker membrane by moderate increase in temperature.
3. Catecholaminic drugs have positive chronotropic effect.
4. Thyroid hormones : have positive chronotropic effect , due to the fact that these drugs increase the sensitivity of adrenergic receptors to adrenaline and noreadrenaline .
5. mild hypoxia.
6. mild alkalemia : mild alkalemia decreases the negativity of the resting potential.
7. hypocalcemia.
8. mild hypokalemia


II. Factors that decrease rhythmicity ( negative chronotropic):


1.Vagal stimulation : the basal level of vagal stimulation inhibits the sinus rhythm and decrease it from 110-75 beats/ minute. This effect due to increasing the permeability of the cardiac muscle cell to potassium , which causes rapid potassium eflux , which increases the negativity inside the cardiac cells (hyperpolarization ).
2. moderate cooling
3. severe warming : due to cardiac damage , as a result of intercellular protein denaturation. Excessive cooling on the other hand decrease metabolism and stops rhythmicity.
4. Cholenergic drugs ( such as methacholine , pilocarpine..etc) have negative chronotropic effect.
5. Digitalis : these drugs causes hyperpolarization . This effect is similar to that of vagal stimulation.
6. Hypercapnia ( excessive CO2 production )
7. Acidemia.
8. hyper- and hyponatremia .
9. hyperkalemia
10. hypercalcemia
11. Typhoid or diphteria toxins.

Red blood cell cycle:

RBCs enter the blood at a rate of about 2 million cells per second. The stimulus for erythropoiesis is the hormone erythropoietin, secreted mostly by the kidney. RBCs require Vitamin B12, folic acid, and iron. The lifespan of RBC averages 120 days. Aged and damaged red cells are disposed of in the spleen and liver by macrophages. The globin is digested and the amino acids released into the blood for protein manufacture; the heme is toxic and cannot be reused, so it is made into bilirubin and removed from the blood by the liver to be excreted in the bile. The red bile pigment bilirubin oxidizes into the green pigment biliverdin and together they give bile and feces their characteristic color. Iron is picked up by a globulin protein (apotransferrin) to be transported as transferrin and then stored, mostly in the liver, as hemosiderin or ferritin. Ferritin is short term iron storage in constant equilibrium with plasma iron carried by transferrin. Hemosiderin is long term iron storage, forming dense granules visible in liver and other cells which are difficult for the body to mobilize.

Some iron is lost from the blood due to hemorrhage, menstruation, etc. and must be replaced from the diet. On average men need to replace about 1 mg of iron per day, women need 2 mg. Apotransferrin (transferrin without the iron) is present in GI lining cells and is also released in the bile. It picks up iron from the GI tract and stimulates receptors on the lining cells which absorb it by pinocytosis. Once through the mucosal cell iron is carried in blood as transferrin to the liver and marrow. Iron leaves the transferrin molecule to bind to ferritin in these tissues. Most excess iron will not be absorbed due to saturation of ferritin, reduction of apotransferrin, and an inhibitory process in the lining tissue.

 

Erythropoietin Mechanism:

Myeloid (blood producing) tissue is found in the red bone marrow located in the spongy bone. As a person ages much of this marrow becomes fatty and ceases production. But it retains stem cells and can be called on to regenerate and produce blood cells later in an emergency. RBCs enter the blood at a rate of about 2 million cells per second. The stimulus for erythropoiesis is the hormone erythropoietin, secreted mostly by the kidney. This hormone triggers more of the pleuripotential stem cells (hemocytoblasts) to follow the pathway to red blood cells and to divide more rapidly.

 

It takes from 3 to 5 days for development of a reticulocyte from a hemocytoblast. Reticulocytes, immature rbc, move into the circulation and develop over a 1 to 2 day period into mature erythrocytes. About 1 to 2 % of rbc in the circulation are reticulocytes, and the exact percentage is a measure of the rate of erythropoiesis.

Transport of Carbon Dioxide

A.    Dissolved in Blood Plasma (7-10%)

B.    Bound to Hemoglobin (20-30%)

1.    carbaminohemoglobin - Carb Dioxide binds to an amino acid on the polypeptide chains

2.    Haldane Effect - the less oxygenated blood is, the more Carb Diox it can carry

a.    tissues - as Oxygen is unloaded, affinity for Carb Dioxide increases
b.    lungs - as Oxygen is loaded, affinity for Carb Dioxide decreases, allowing it to be released

C.    Bicarbonate Ion Form in Plasma (60-70%)

1.    Carbon Dioxide combines with water to form Bicarbonate

CO2 + H2O <==> H2CO3 <==> H+ + HCO3-

2.    carbonic anhydrase - enzyme in RBCs that catalyzes this reaction in both directions

a.    tissues - catalyzes formation of Bicarbonate
b.    lungs - catalyzes formation of Carb Dioxide

3.    Bohr Effect - formation of Bicarbonate (through Carbonic Acid) leads to LOWER pH (H+ increase), and more unloading of Oxygen to tissues

a.    since hemoglobin "buffers" to H+, the actual pH of blood does not change much

4.    Chloride Shift - chloride ions move in opposite direction of the entering/leaving Bicarbonate, to prevent osmotic problems with RBCs

D.    Carbon Dioxide Effects on Blood pH

1.    carbonic acid-bicarbonate buffer system
    
low pH       → HCO3- binds to H+
high pH     →   H2CO3 releases H+
    
2.     low shallow breaths    → HIGH Carb Dioxide    → LOW pH (higher H+)
3.     rapid deep breaths     → LOW Carb Dioxide   → HIGH pH (lower H+)

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